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Gene Review

XAF1  -  XIAP associated factor 1

Homo sapiens

Synonyms: BIRC4-binding protein, BIRC4BP, HSXIAPAF1, XIAP-associated factor 1, XIAPAF1
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Disease relevance of XAF1


High impact information on XAF1

  • Expression of XAF1 triggers a redistribution of XIAP from the cytosol to the nucleus [7].
  • XAF1 is ubiquitously expressed in normal tissues, but is present at low or undetectable levels in many different cancer cell lines [7].
  • Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells [7].
  • XIAP suppresses caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities [7].
  • The aim of this study was to examine the novel pattern of methylation of XAF1 in gastric and colon cancers and locate the important CpG sites for transcriptional regulation and tumor progression [2].

Chemical compound and disease context of XAF1


Biological context of XAF1


Anatomical context of XAF1

  • Examination of the same NCI cell line panel for xaf1 RNA expression demonstrated that cancer cell lines exhibited very low levels of mRNA relative to normal human liver [8].
  • The regulation of IAPs and XAF1 varied after axotomy of the sciatic nerve; in the neonate, there was a significant loss of IAP in the injured motoneurons as opposed to the adult, in which there was only a moderate decrease [9].

Associations of XAF1 with chemical compounds

  • Methylation status of XAF1 was determined by methylation-specific PCR (MSP) and bisulfite DNA sequencing PCR analysis [2].
  • XAF1 expression enhanced the apoptotic response of tumor cells to chemotherapeutic agents, such as etoposide or 5-FU [10].

Physical interactions of XAF1

  • Moreover, pretreatment with antioxidants suppressed HSF1 binding activity and increased the transcriptional activity and expression of XAF1 [5].
  • Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family [7].

Regulatory relationships of XAF1

  • Both the caspase inhibiting and the anti-apoptotic abilities of XIAP were found to be blocked by overexpressed XAF1 [8].
  • HSF1 down-regulates XAF1 through transcriptional regulation [5].
  • This implicates a role for the mitochondrial apoptotic pathway, consistent with the ability of Bcl2 to block Xaf1 induced apoptosis [11].

Other interactions of XAF1

  • We propose that a high level of XIAP to XAF1 expression in cancer cells may provide a survival advantage through the relative increase of XIAP anti-apoptotic function [8].
  • The xaf1 locus was further refined to YAC 746C10, approximately 3 cM distal to TP53 [8].
  • These results suggested that IFN-dependent induction of XAF1 strongly influenced cellular sensitivity to the proapoptotic actions of TRAIL [4].
  • The expression of XAF1 and HSF1 was negatively correlated in gastrointestinal cancer cell lines [5].
  • However, IFNs induced high levels of XAF1 protein predominantly in cell lines sensitive to the proapoptotic effects of IFN-beta [4].

Analytical, diagnostic and therapeutic context of XAF1


  1. All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer. Wang, J., Peng, Y., Sun, Y.W., He, H., Zhu, S., An, X., Li, M., Lin, M.C., Zou, B., Xia, H.H., Jiang, B., Chan, A.O., Yuen, M.F., Kung, H.F., Wong, B.C. Gastroenterology (2006) [Pubmed]
  2. Correlation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers. Zou, B., Chim, C.S., Zeng, H., Leung, S.Y., Yang, Y., Tu, S.P., Lin, M.C., Wang, J., He, H., Jiang, S.H., Sun, Y.W., Yu, L.F., Yuen, S.T., Kung, H.F., Wong, B.C. Gastroenterology (2006) [Pubmed]
  3. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas. Byun, D.S., Cho, K., Ryu, B.K., Lee, M.G., Kang, M.J., Kim, H.R., Chi, S.G. Cancer Res. (2003) [Pubmed]
  4. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. Leaman, D.W., Chawla-Sarkar, M., Vyas, K., Reheman, M., Tamai, K., Toji, S., Borden, E.C. J. Biol. Chem. (2002) [Pubmed]
  5. HSF1 down-regulates XAF1 through transcriptional regulation. Wang, J., He, H., Yu, L., Xia, H.H., Lin, M.C., Gu, Q., Li, M., Zou, B., An, X., Jiang, B., Kung, H.F., Wong, B.C. J. Biol. Chem. (2006) [Pubmed]
  6. Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses. Chung, S.K., Lee, M.G., Ryu, B.K., Lee, J.H., Han, J., Byun, D.S., Chae, K.S., Lee, K.Y., Jang, J.Y., Kim, H.J., Chi, S.G. Gastroenterology (2007) [Pubmed]
  7. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Liston, P., Fong, W.G., Kelly, N.L., Toji, S., Miyazaki, T., Conte, D., Tamai, K., Craig, C.G., McBurney, M.W., Korneluk, R.G. Nat. Cell Biol. (2001) [Pubmed]
  8. Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Fong, W.G., Liston, P., Rajcan-Separovic, E., St Jean, M., Craig, C., Korneluk, R.G. Genomics (2000) [Pubmed]
  9. Motoneuron resistance to apoptotic cell death in vivo correlates with the ratio between X-linked inhibitor of apoptosis proteins (XIAPs) and its inhibitor, XIAP-associated factor 1. Perrelet, D., Perrin, F.E., Liston, P., Korneluk, R.G., MacKenzie, A., Ferrer-Alcon, M., Kato, A.C. J. Neurosci. (2004) [Pubmed]
  10. Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses. Lee, M.G., Huh, J.S., Chung, S.K., Lee, J.H., Byun, D.S., Ryu, B.K., Kang, M.J., Chae, K.S., Lee, S.J., Lee, C.H., Kim, J.I., Chang, S.G., Chi, S.G. Oncogene (2006) [Pubmed]
  11. Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP. Xia, Y., Novak, R., Lewis, J., Duckett, C.S., Phillips, A.C. Mol. Cell. Biochem. (2006) [Pubmed]
  12. Low expression of XIAP-associated factor 1 in human colorectal cancers. Ma, T.L., Ni, P.H., Zhong, J., Tan, J.H., Qiao, M.M., Jiang, S.H. Chinese journal of digestive diseases. (2005) [Pubmed]
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